Infectious and parasitic diseases' account for 40% of the total mortality in developing countries, and a significant proportion of these are diseases such as yellow fever, malaria, filariasis, dengue, and encephalitis--all carried by mosquitoes. The morbidity and debility caused by vector-borne diseases exert a devastating toll on the global economy. This situation is exacerbated by the escalating cost of insecticides for the control of vectors that display ever-increasing levels of chemical resistance. More effective control strategies are urgently needed; these can be most rationally and effectively designed if the physiology and behavior of the vector are taken into consideration. The current application is for the continuation of a project that has as its overall goal the elucidation of the mechanisms that control odor-mediated behaviors in the mosquito. Such behaviors include host-seeking, oviposition, and plant feeding and are of critical importance in mosquito reproduction and epidemiological competence. Host-seeking is the long-distance orientation of the female to host volatiles and is modulated during the gonotrophic cycle by endogenous factors that act on the peripheral sensory system in such a way as to render the female functionally anosmic to the host attractant lactic acid. We have made progress in isolating and identifying the endogenous factors that prevent long-range host attraction in Aedes aegypti, and we have incorporated our observations of host-seeking and other behaviors into a neurophysiological model of behavioral control that explains differential behavioral expression in this species. Our specific aims in this application are to test the predictions of our model in other species of mosquitoes and to continue our work on the purification and characterization of the endogenous inhibitors of host-seeking.